Figure 3.

Pathway for 11-oxygenated androgen synthesis, which begins in the adrenal cortex. Androstenedione and testosterone are produced by the classical pathway (figure 2). Dehydroepiandrosterone is diverted to downstream androgens or sulphonated to dehydroepiandrosterone sulphate by the sulphotransferase, SULT2A1. Androstenedione and testosterone are hydroxylated by 11β-hydroxylase (CYP11B) to produce abundant 11β-hydroxyandrostenedione (11OHA4) and smaller amounts of 11β-hydroxytestosterone (11OHT). Renal 11β-hydroxysteroid dehydrogenase type 2 (HSD11B2) converts 11OHT to 11-ketotestosterone (11KT) and 11OHA4 to 11-ketoandrostenedione (11KA4). In adipose tissue, 11KA4 is metabolised to 11KT and 11-ketodihydrotestosterone (11DHKT) by aldo-keto reductase type 1C3 (AKR1C3) and steroid-5α-reductase (SRD5A), respectively. 11OHA4 is metabolised to 11OHT and 11β-hydroxydihydrotestosterone (11OHDHT) by 17β-hydroxysteroid dehydrogenase 2 (HSD17B2) and SRD5A, respectively. 11KT and 11KDHT are potent agonists of the androgen receptor whereas 11OHT and 11OHDHT have milder potency. StAR=steroidogenic acute regulatory protein; HSD3B2=3β-hydroxysteroid dehydrogenase type II; CYP11A1, CYP17A1, CYP11B1=cytochrome P450 enzymes